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2006 Grant - Robertson

Neurotrophin-3: Maintenance of Cholinergic Circuitry

Richard T. Robertson, Ph.D.University of CaliforniaIrvine, California

2006 Investigator-Initiated Research Grant

Alzheimer's disease is characterized by the degeneration and eventual death of specific types of neurons in the brain called cholinergic neurons. These use a chemical messenger called acetylcholine to communicate with each other and with other cells. As Alzheimer's disease progresses, these cholinergic neurons start losing synapses, specialized junctions between neurons that facilitate cell-to-cell communication. Synapse loss is believed to cause the memory failures associated with the disease. Eventually, these cholinergic neurons themselves begin to die.

There is evidence that certain proteins in the brain called neurotrophins can help protect cholinergic cells from damage. Much research has focused on a neurotrophin called nerve growth factor, but Richard Robertson, Ph.D, believes that a different protein called neurotrophin-3 (NT-3) may also protect the neurons from damage.

Robertson and colleagues plan to test this theory using laboratory rats that have damaged cholinergic "circuitry." The researchers will administer NT-3 into the brain of these animals over a four-week period, after which the animals will be evaluated in tests of learning and memory. Following this behavioral test, the brains of the animals will be examined to determine if NT-3 has had any effect on the quantity or quality of the cholinergic cells. This work could identify a potentially valuable therapeutic approach to pre-vent or repair damage to neurons that are vulnerable in Alzheimer's disease.